Documenta Ophthalmologica最新文献

Purpose: To provide a conceptual understanding of the continuous and discrete wavelet transforms (CWT, DWT) for clinical electroretinography (ERG) analysis, and how these methods uncover time-frequency features that complement traditional time-domain analysis.

Methods: A technical overview without the use of mathematical formula describing the basics of CWT and DWT and implementation considerations. We also review an example of four standard ISCEV full-field ERG (ffERG) recordings from a healthy 32-year-old male.

Results: Wavelet analysis uncovered time-frequency signatures absent in raw traces. In DA 0.01 cd s/m² DWT scalogram, energy localized in the 2-5 Hz range, with CWT scalograms corroborating these findings. In DA 3.0 cd s/m², a broader frequency response is seen across 10, 20 and 40 Hz center frequencies. A similar progression was found in the LA 3.0 cd s/m², with additional low energy indices at 80 and 160 Hz. For the LA 30 Hz flicker, all frequency and time-frequency profiles effectively replicated the 30 Hz response of the cone system.

Conclusions: CWT and DWT provide complementary and objective insight into ERG responses. Open-source MATLAB toolkit and step-by-step tutorial provided herein lower technical barriers and enable use by the broader community.

Purpose: To describe multimodal imaging and electrophysiology features of CTNNA1-associated retinal dystrophy in a family with p.(Leu318Ser) substitution.

Methods: Three family members including a 48-year-old male proband, his 52-year-old sister, and their 67-year-old mother, were evaluated with multimodal imaging and electrophysiology. The proband, referred with suspected Best's disease, underwent a retinal dystrophy panel and two affected family members were target sequenced for the familial variant.

Results: The NM_001903.5:c.953T > C variant in CTNNA1 segregated with affected family members. They maintained a visual acuity of 20/25 or better throughout 2-4 years of follow-up. The proband exhibited butterfly-shaped pigment dystrophy whilst his sister had no macular lesions, and their mother had foveal pigmentary changes. All three displayed peripheral retinal reticular pigmentation with variable atrophy. Microperimetry demonstrated enlarging paracentral scotoma in the proband whilst Esterman binocular suprathreshold test showed reproducible peripheral loss in the proband's sister. Multifocal electroretinography (ERG) confirmed central macular dysfunction in the proband. In all three, full-field ERG showed mildly delayed dark-adapted (DA) 0.01 b-wave and DA3.0 a-wave, and a light-rise of < 1.7 in one or both eyes on electro-oculography (EOG).

Conclusions: CTNNA1-associated retinal dystrophy due to p.(Leu318Ser) has a unique peripheral retinal phenotype despite variable macular involvement. Reduced EOG light-rise and peripheral reticular pigmentation should raise suspicion of CTNNA1 in butterfly-shaped pigment dystrophy.

Purpose: The photopic negative response (PhNR) and pattern ERG, both established electrophysiological measures of retinal ganglion cell (RGC) function, are recorded under photopic conditions. The purpose of this study was to describe the mesopic negative response (MeNR), a novel marker of RGC function within the rod pathway.

Methods: Ten visually-normal controls (mean age ± SD 54.6 ± 5.6 years) and 12 patients with severe primary open-angle glaucoma (mean age ± SD 58.4 ± 4.9 years) participated. Light-adapted, full-field ERGs were elicited by a rod-isolating pulse generated on the principle of silent substitution (0.46 scot. cd/m²; 55% contrast; 40 ms) presented against a steady background (0.30 scot. cd/m²). In addition, (1) the PhNR was recorded; (2) subjects were dark-adapted for 20 min and the ISCEV DA 0.01 was recorded.

Results: The normal rod-isolated pulse response was characterized by a positive potential at 85 ms followed by a slow negative potential (MeNR) at 175 ms following the pulse. The mean (± SEM) amplitude of the positive potential was similar for the control (13.4 ± 1.2 µV) and glaucoma (11.6 ± 1.35 µV) groups (p = 0.33), and was correlated with the DA 0.01 amplitude (r = 0.71, p < 0.001). The amplitude of the MeNR was significantly (p < 0.001) attenuated for the glaucoma group (4.5 ± 0.7 µV) compared to the controls (9.7 ± 1.25 µV), and was correlated with the PhNR amplitude (r = 0.86, p < 0.001).

Conclusions: Rod-isolated ERGs can be obtained without dark-adaptation using silent-substitution. The positive potential and MeNR of the rod-isolated response appear to be generated by rod bipolar cells and RGCs, respectively. In severe glaucoma, the positive (bipolar cell) potential was not significantly affected, whereas the MeNR was significantly reduced. MeNR analysis may be useful for studying RGC function within the rod pathway.

Purpose: To report a rare case of bilateral idiopathic multifocal retinal pigment epithelial detachments (imfPEDs) and to describe the long-term morphological and functional changes observed over a 16-year follow-up period.

Methods: A 49-year-old woman was diagnosed with imfPEDs based on multimodal imaging, including optical coherence tomography (OCT), fluorescein angiography (FA), and fundus photography. Full-field electroretinograms (ffERGs) and multifocal ERGs (mfERGs) were recorded to assess retinal function. The patient voluntarily discontinued follow-up but returned 16 years later due to cataract progression. Retinal morphology and function were re-evaluated using comparable multimodal imaging and electrophysiological methods.

Results: At the initial visit, multiple bilateral pigment epithelial detachments (PEDs) were identified. OCT showed hyporeflective, dome-shaped PEDs with smooth borders, and ERG responses were within normal limits. Sixteen years later, some PEDs had resolved, others had newly developed or fused, and geographic atrophy was observed, particularly in the peripheral retina. Fundus autofluorescence (FAF), performed in place of FA, revealed hyperautofluorescent PEDs and numerous peripheral hypofluorescent spots. ffERGs remained normal, while mfERGs showed localized attenuation with relatively preserved macular function. These findings were consistent with large colloid drusen and cuticular drusen.

Conclusion: This case demonstrates the slow morphological progression and relative functional preservation in bilateral imfPEDs over 16 years. Comparable multimodal imaging and electrophysiological testing were valuable in monitoring the long-term clinical course and support the classification of this phenotype as a variant of large colloid or cuticular drusen.

Purpose: To report a case of hereditary spherocytosis (HS) carrying a pathogenic variant in the SPTB gene, presenting with angioid streaks (ASs) and central retinal dysfunction.

Methods: A 63-year-old female patient diagnosed with HS was evaluated using multimodal imaging, full-field and multifocal electroretinograms (ffERGs and MfERGs), and genetic testing with an HS gene panel.

Results: Her best-corrected visual acuity was Snellen equivalent 20/22 in the right eye and 20/20 in the left eye. Fundus examination revealed ASs with chorioretinal atrophy around the optic discs in both eyes (OU). Fundus autofluorescence imaging showed areas of autofluorescence loss corresponding to ASs and chorioretinal atrophy. In the ffERGs, dark-adapted (DA) 0.01 b-wave amplitudes and DA 3.0/10.0 a-wave amplitudes were nearly normal, but b-wave amplitudes were slightly reduced in OU. Meanwhile, light-adapted (LA) 3.0 a- and b-wave amplitudes, as well as the LA 30 Hz flicker amplitudes, were slightly reduced. The mfERG trace arrays showed amplitude reductions, particularly in the central to temporal regions in OU. Genetic testing identified a heterozygous splice-site variant (c.4973 + 5G > A) in SPTB (NM_001355436.2), classified as likely pathogenic.

Conclusions: This is the first reported case of an HS patient with ASs associated with an SPTB variant, exhibiting mild cone system dysfunction accompanied by central retinal dysfunction.

Purpose: To investigate the effects of brief flickering light stimulation (FLS) on retinal electrophysiology and retinal blood flow (RBF) in normal C57BL6J mice.

Methods: RBF and full-field electroretinography (ffERG) were measured before and after a 60 second FLS (12 Hz, 0.1 cd·s/m²) in a cohort of 8-12-weeks old C57BL6J mice (n=10) under anaesthetic and light-adapted conditions. A separate set of age-matched mice (n=9) underwent RBF and ffERG measurements before and after steady light stimulation (SLS) at 1 cd/m² under similar conditions. The changes in RBF (arterial and venous flow) as well as the amplitudes and implicit times of the a-wave, b-wave, oscillatory potentials (OPs), and photopic negative response (PhNR) were analyzed.

Results: FLS significantly increased both arterial (p=0.003) and venous (p=0.018) blood flow as well as b-wave amplitudes (p=0.017) compared to SLS, which did not have any significant changes in either RBF or ERG. However, no significant differences were found in other ffERG responses (amplitudes and implicit times of a-wave, OPs, and PhNR, as well as b-wave implicit time) between the two groups after light stimulation. An increase in b-wave amplitude was positively associated with an increase in both arterial (r=0.655, p=0.040) and venous blood flow (r=0.638, p=0.047) in the FLS group.

Conclusions: Our results suggest that transient FLS not only increases RBF but also enhances electro-retinal responses of the middle retinal layer, as shown by ffERG, thus demonstrating its substantial effects on both the vascular and neuronal components of retinal neurovascular coupling in mice.

Purpose: Landrace pigs are increasingly used as a large-animal model in ophthalmic research due to their cone-enriched visual streak and anatomical similarity to the human eye. However, they are commonly studied at 16-20 weeks of age, a timeframe in which the animals double their weight and development-related physiological changes may occur. This study aims to characterize retinal function and morphology and establish reference values for future translational studies.

Methods: Landrace pigs (16-20 weeks old) underwent standardized examinations of the left eye at baseline (16 weeks), 18 and 20 weeks. The left eye was examined by optical coherence tomography (OCT), fundus photography, histology, and full-field electroretinography (ffERG) under light- and dark-adapted conditions, using the ISCEV-compliant 6-step Dog, Cat, Nonhuman Primate protocol.

Results: A total of 30 animals were included. Retinal morphology remained stable throughout the study period, with no significant changes in retinal thickness observed by OCT (baseline: 252 ± 24 µm; week 20: 249 ± 11 µm; p = 0.17) or by histology. ffERG revealed increased amplitudes under light- and dark-adapted conditions at 20 weeks compared to baseline at 16 weeks of age (e.g. light-adapted b-wave: + 65 µV, + 18.4%, p < 0.01), while latencies remained stable without clinically relevant changes.

Conclusions: During this phase of rapid development, Landrace pigs undergo significant functional retinal maturation without corresponding morphological changes emphasizing importance of functional testing in retinal assessments. This study provides reference data in a large number of animals.

Purpose: To evaluate subjective and objective macular retinal function and morphology in eyes after autologous retinal transplantation (ART).

Methods: We conducted the study in three patients with large macular holes (MHs) who underwent ART. The examination modalities included optical coherence tomography (OCT), microperimetry (MP-3), and focal macular electroretinography (FMERG) with 10-degree and 5-degree stimulus spots under infrared camera monitoring centered on the treated MHs after ART.

Results: All three patients showed improved visual acuity after the ART; MP-3 showed relatively good sensitivity around the fixation point with a dense scotoma at the center of the graft. All MHs were closed with autologous grafts and the size of MHs was decreased. OCT revealed clearly visible ellipsoid zones of the host retina around the grafted retina, however one transplanted eye showed disorganized outer layer of the host retina near the border of graft-host retina. FMERGs with the 10-degree stimulus were recorded successfully in all three treated eyes with more than half of a- and b-wave amplitudes of the fellow eyes. FMERGs with the 5-degree stimulus were recorded successfully in two of the treated and their fellow eyes.

Conclusions: The FMERGs showed well-maintained macular retinal function after ART. The electrophysiologic and anatomic outcomes suggested that the host retina around the transplanted retina may play an important role in the postoperative macular retinal function with the mechanical support by the graft.

Introduction: Retinal dysfunction associated with CACNA2D4 gene defects is a rare disorder of photoreceptor to bipolar cell signaling. We report two affected siblings presenting a surprising disparity of retinal involvement.

Materials and methods: Patients underwent complete ocular examination, multimodal fundus imaging, and full-field electroretinography (ffERG). Genetic testing was performed by a targeted Next Generation Sequencing panel.

Results: Two siblings presented a reduced visual acuity and light sensitivity. ffERG was specific for CACNA2D4-related retinal dysfunction, but amplitudes of responses were different in the two patients. Additionally, an x-wave to a dim red flash was well preserved, and there was a reduced b/a ratio to a high intensity (30cd/m2) dark-adapted stimulus. Both patients were homozygous for the variant c.2406C > A, p.(Tyr802*) in CACNA2D4. During 17 years of follow-up, vision remained stable in patient 1, with no evidence of retinal degeneration.

Conclusion: Intrafamily clinical and electrophysiological expression of CACNA2D4-associated retinal dysfunction can be variable.

Purpose: This case report aims to describe an atypical presentation of pigmented paravenous chorioretinopathy (PPCRA).

Methods: Detailed clinical ophthalmologic examinations, multimodal imaging and electroretinography of a 33-year-old woman who presented with unilateral PPCRA.

Results: A 33-year-old female who is known to have hypothyroidism and had previous bariatric surgery, referred for retinal evaluation following incidental findings during a refractive surgery consultation. Fundus examination revealed unilateral segmental perivascular hyperpigmentation, vascular sclerosis, and areas of chorioretinal atrophy, raising the differential diagnosis of pigmented paravenous chorioretinopathy (PPCRA) versus resolved retinal vasculitis. The patient reported no significant ocular symptoms apart from decreased night vision in one eye and denied a history of acute visual loss or photophobia. Systemic workup, including autoimmune and infectious serologies, imaging, and a detailed clinical history, was unremarkable. The patient reported consanguinity within the family.

Conclusion: This report underscores the challenge of distinguishing PPCRA, a rare, typically bilateral hereditary condition, from resolved vasculitis, which often presents unilaterally with a history of systemic inflammation. Fluorescein angiography and optical coherence tomography were instrumental in identifying the lack of active inflammation and vascular leakage, favoring the diagnosis of PPCRA.